Host defense to pathogens and other antigens is dependent upon mononuclear cell recruitment, activation and finally, downregulation. This research project focuses on delineating the cellular and molecular mechanisms controlling these events. Whereas blood monocytes readily respond to inflammatory chemotactic stimuli, mononuclear phagocytes from within inflammatory sites exhibit defective chemotactic activity due to loss of chemotactic ligand (C5a) receptors. Increased monocyte maturation as reflected by increased HLA-DR was found to be associated with decreased chemotaxis receptor expression providing a mechanism for macrophage accumulation within an inflammatory site. Once within the inflammatory site, macrophages are induced to express CD16 (Fc gammaR111) by the inflammatory cytokine, TGF-beta. Signal transduction through this receptor regulates immunophagocytosis and can promote tissue destruction through the release of reactive oxygen intermediates (ROI). The ability of TGF-beta to stimulate monocyte phenotypic and functional changes is transient since TGF-beta receptors are lost during differentiation. Additional mechanisms of immune suppression may occur through the release of IL-4 which can suppress TGF-beta-induced Fc gammaR111 expression, inhibit ROI, and downregulate monokine production. Thus, immune cell-derived cytokines provide a series of intercellular signals which initiate, augment and ultimately, suppress the immune response.